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However, it remains unclear how disruption of the circadian clock modulates molecular aspects of innate immune responses, including inflammasome signaling. Here, we examined the potential role of the circadian clock in inflammasome-mediated responses through myeloid-specific deletion of BMAL1, a master circadian clock regulator. Intriguingly,\n                    <jats:italic>Bmal1<\/jats:italic>\n                    deficiency significantly enhanced pyroptosis of macrophages and lethality of mice under noncanonical inflammasome-activating conditions but did not alter canonical inflammasome responses. Transcriptome analysis of enriched peritoneal myeloid cells revealed that\n                    <jats:italic>Bmal1<\/jats:italic>\n                    deficiency led to a marked reduction in Rev-erb\u03b1 expression at steady state and a significant increase in serum amyloid A1 (SAA1) expression upon poly(I:C) stimulation. Notably, we found that the circadian regulator Rev-erb\u03b1 is critical for poly(I:C)- or interferon (IFN)-\u03b2-induced SAA1 production, resulting in the circadian oscillation pattern of SAA1 expression in myeloid cells. Furthermore, exogenously applied SAA1 markedly increased noncanonical inflammasome-mediated pyroptosis of macrophages and lethality of mice. Intriguingly, our results revealed that type 1 IFN receptor signaling is needed for poly(I:C)- or IFN-\u03b2-induced SAA1 production. Downstream of the type 1 IFN receptor, Rev-erb\u03b1 inhibited the IFN-\u03b2-induced association of C\/EBP\u03b2 with the promoter region of\n                    <jats:italic>Saa1<\/jats:italic>\n                    , leading to the reduced transcription of\n                    <jats:italic>Saa1<\/jats:italic>\n                    in macrophages.\n                    <jats:italic>Bmal1<\/jats:italic>\n                    -deficient macrophages exhibited enhanced binding of C\/EBP\u03b2 to\n                    <jats:italic>Saa1<\/jats:italic>\n                    . Consistently, the blockade of Rev-erb\u03b1 by SR8278 significantly increased poly(I:C)-stimulated SAA1 transcription and noncanonical inflammasome-mediated lethality in mice. Collectively, our data demonstrate a potent suppressive effect of the circadian clock BMAL1 on the noncanonical inflammasome response via the Rev-erb\u03b1-C\/EBP\u03b2-SAA1 axis.\n                  <\/jats:p>","DOI":"10.1038\/s12276-024-01162-w","type":"journal-article","created":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T21:22:22Z","timestamp":1706736142000},"page":"370-382","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Deficiency of circadian clock gene Bmal1 exacerbates noncanonical inflammasome-mediated pyroptosis and lethality via Rev-erb\u03b1-C\/EBP\u03b2-SAA1 axis"],"prefix":"10.1038","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1893-8323","authenticated-orcid":false,"given":"Do-Wan","family":"Shim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Cheol","family":"Eo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saeyoung","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inhwa","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"BoYoung","family":"Nam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Eun","family":"Shin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7923-5635","authenticated-orcid":false,"given":"Seung Hyeok","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Je-Wook","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,1]]},"reference":[{"key":"1162_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1740-3391-8-3","volume":"8","author":"S Rana","year":"2010","unstructured":"Rana, S. & Mahmood, S. 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